In vitro diagnostics (IVD) allows labs to assist in the diagnosis of disease based on assays performed on patient fluid samples. IVD includes various types of analytical tests and assays related to patient diagnosis and therapy that can be performed by analysis of a liquid sample taken from a patient's bodily fluids, or abscesses. These assays are typically conducted with automated clinical chemistry analyzers (analyzers) onto which fluid containers, such as tubes or vials containing patient samples have been loaded. The analyzer extracts a liquid sample from the vial and combines the sample with various reagents in special reaction cuvettes or tubes (referred to generally as reaction vessels). In some conventional systems, a modular approach is used for analyzers. A lab automation system can shuttle samples between one sample processing module (module) and another module. Modules may include one or more stations, including sample handling stations and testing stations (e.g., a unit that can specialize in certain types of assays or can otherwise provide testing services to the larger analyzer), which may include immunoassay (IA) and clinical chemistry (CC) stations. Some traditional IVD automation track systems comprise systems that are designed to transport samples from one fully independent module to another standalone module. This allows different types of tests to be specialized in two different stations or allows two redundant stations to be linked to increase the volume of sample throughput available.
There has been an increasing trend in the in vitro diagnostics (IVD) industry to combine multiple testing modalities into a single integrated system. For example, clinical chemistry, which tests for levels of potassium, sodium, etc., can be combined with immunoassays, hematology, or various different testing modalities. The testing stations can be connected either through automation or through integrated analyzers that have different analytical cores. These systems are typically part of big labs where technicians transfer sample tubes from one location to another. Individual samples in the tubes may be subjected to broad test panels, requiring multiple tests on each sample.
In some conventional systems, carrier mechanisms (carriers), which can include pucks (typically containing a single sample vessel) or racks (typically containing a plurality of sample vessels) shuttle sample vessels between different stations. Samples may be stored in sample vessels/containers, such as test tubes, that are placed into a carrier by an operator or a place and pick device for transport between stations in an analyzer along the track. The place and pick device is used to unload individual test tubes from the carriers to the tube storage area and load individual test tubes from a tube storage area onto the carriers.
When addressing multiple modalities in a test panel, a sample tube typically has to be processed serially by a plurality of stations within the lab or within the analyzer, which can significantly increase the turnaround time. One way to overcome this problem is by making an aliquot of the primary sample, splitting the sample into multiple daughter test tubes and then processing each daughter tube in parallel on a different analyzer. This can allow for parallel processing subsequent to the aliquoting process.
The benefits of parallel processing are only realized, however, if testing modules hold a tube captive for a long amount of time (the capture time). If a tube is only held briefly at each module and the travel time between modules is short, then the extra time required to aliquot daughter tubes may actually increase the overall turnaround time (TAT). The percentage of tubes that would benefit from aliquoting is primarily dependent on the architecture of the IVD system. Furthermore, making a daughter tube requires extra consumables (e.g., sterile tubes to be filled) and extra equipment (such as a dedicated aliquoting station), which increases the per-test cost. Due to the upfront cost, disposables cost/hassle, and increased footprint of a dedicated aliquoter module, many systems that would occasionally benefit from aliquoting simply forgo the functionality entirely. The ability to use existing, multi-function hardware to perform low volume aliquoting on IVD systems is a currently unmet need in the industry.
Both transport time and capture time determine if a system would benefit from the parallelism of daughter tubes. However, traditionally the transport time is a lot less than the capture time, because most systems are either traditional track based systems (typically having large queues of tubes waiting to be processed) or standalone analyzers (where once you load a tube you cannot unload it until an entire batch had been processed). Because the amount of time that the tube is held captive is typically very large compared to transit time, many systems may not warrant using an aliquoting station.
Another potential reason for making an aliquot is if the test being performed by an analyzer could contaminate the primary sample (e.g., if a test is not zero carryover). For instance, some analyzers use disposable pipettor tips, which ensures that there is no carryover between one sample and the next. These are usually analyzers that are very sensitive to carryover and can give a false reading any time there is even a small amount of contamination. Other analyzers are a lot more robust against contamination, so not all analyzers have a zero carryover pipettor. However, if a test tube goes from a low sensitivity analyzer to a high sensitivity analyzer, the primary sample may have been contaminated from the point of view of the high sensitivity analyzer. If one does not make discrete aliquots of such a sample, the lab must to be very careful about the order of processing the tube through multiple analyzers. If there are any follow-on tests or add-on orders afterwards, this contamination can create a serious problem, perhaps even requiring a redraw to get a new primary sample from a patient. A daughter aliquot is if there is some testing that you cannot do locally, you have to outsource it. Also, if something needs to be centrifuged or chilled before a test, it may make sense to use an aliquot from the primary sample.
These problems with unaliquoted samples are not commonly addressed because these situations tend to be the exception. Taking the time to aliquot from the majority of tubes typically will not provide much benefit. The benefits of aliquoting a sample depend on how the analyzers are set up, how the lab is set up, and the sensitivity and the overall technology. As the systems mature, there are some samples where it is desirable to perform an aliquot and some samples where it is not. Using a dedicated aliquoter, which is how aliquoting is normally performed, requires a dedicated piece of equipment that has its own failure rate, its own consumables, and its own space and dedicated cost. Therefore, labs tend to only have a dedicated aliquoter if they need a very high percentage of tubes to be aliquoted. If they do not need a larger percentage of tubes to be aliquoted, they normally rely on manual aliquots or just accept the loss in time or performance.
The prior art does not generally address situations where a small percentage of tubes would benefit from aliquoting. The art does not adequately address special cases where you want aliquoting, but not for the majority of your tubes. Different companies have tried different systems that have made different tradeoffs. For example, some systems include a dedicated aliquoting module. Historically, this approach has been used in systems that transport tubes in racks, allowing the automation systems to transport multiple tubes together in one fixed carrier, such as five tubes in a rack. These racks significantly increase the amount of time that tubes could be held captive at each module. Other systems are designed to minimize the amount of time that a tube is held captive in order to minimize the need for aliquoting. For example, these systems may utilize clinical chemistry (CC) modules that take local aliquots from the sample tube in order to release the tube as quickly as possible. Instead of using another tube for an aliquot, those systems simply draw enough sample out of the primary tube into a local tube, a local well, or a vial that is kept as a consumable or as a reusable item within the module, and the module will then process the local aliquot so that the primary tube could be released almost instantaneously. Additionally, some automation systems transport tubes in individual pucks, further reducing hold time. The basic industry breakdown to date has been that some companies have dedicated aliquoters, some analyzers do local aliquots without creating daughter tubes, and some companies sample directly out of the tubes to do all their processing.